The oncogenic role of hepatitis delta virus in hepatocellular carcinoma

Abstract

Hepatitis delta virus (HDV) is a small defective virus that needs hepatitis B virus (HBV) to replicate and propagate. HDV infection affects 20-40 million people worldwide and pegylated interferon (PegIFN) is the only recommended therapy. There is limited data on the contribution of HDV infection to HBV-related liver disease or liver cancer. Evidence from retrospective and cohort studies suggests that HBV/HDV coinfection accelerates progression to cirrhosis and is associated with an increased risk of hepatocellular carcinoma (HCC) development compared to HBV monoinfection. Although the life cycle of HDV is relatively well known, there is only ancillary information on the molecular mechanisms that can drive specific HDV-related oncogenesis. No thorough reports on the specific landscape of mutations or molecular classes of HDV-related HCC have been published. This information could be critical to better understand the uniqueness, if any, of HDV-related HCC and help identify novel targetable mutations. Herein, we review the evidence supporting an oncogenic role of HDV, the main reported mechanisms of HDV involvement and their impact on HCC development.

The genomic landscape of Mongolian hepatocellular carcinoma

“…10 and Supplementary Data 12), which is consistent with the hypothesis that a combination of activation of multiple oncogenes and/or tumor suppressor genes may be needed to drive hepatocarcinogenesis. While we found different frequencies of driver mutations in HDV-associated HCC, the oncogenic roles of HDV in HCC could only be speculated 38 . Taken together, these analyses suggest the existence of unique driver mutations linked to Mongolian HCC.…”

Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma

“…Approximately 80% of HCC cases arise from hepatocyte injury and chronic inflammation resulting in cirrhosis[ 6 , 58 ]. HCC in chronic hepatitis B, C, or HBV/HDV co-infection patients occurs in the presence of cirrhosis[ 59 , 60 ]. In contrast, 10%-20% of HBV-related HCC can occur in the absence of cirrhosis and liver inflammation[ 61 ].…”

Cirrhotic controls in a pooled analysis of hepatitis D and hepatocellular carcinoma

“…The role of HDV infection in hepatocarcinogenesis remains a topic of debate and HDV is currently considered "not classifiable as to its carcinogenicity to humans" by the International Agency for Research on Cancer. 1 Relatively few HBV carriers are coinfected with HDV, 2 therefore, single studies on HDV and hepatocellular carcinoma (HCC) are often underpowered to assess this association. 3 In such situations, a meta-analysis or pooled analysis may be useful.…”

“…2 HBV/HDV coinfection results in greater liver inflammation than HBV monoinfection, leading to accelerated development of cirrhosis and likely to HCC. 2 Cirrhosis and HCC are considered final stages of HDVassociated liver disease and many patients with HCC also have cirrhosis. 2 If cirrhosis and HCC are related outcomes resulting from hepatic inflammation, patients with cirrhosis are not an appropriate comparison group for examining HDV-associated hepatocarcinogenesis.…”